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Pathology of the hereditary colorectal carcinoma.
Fam Cancer. 2008; 7(1):15-26.FC

Abstract

Positive familial history (first or second degree relative) for colorectal carcinoma (CRC) can be found in approximately 30% of all newly diagnosed cases, but less than 5% will be due to a defined genetic category of hereditary CRC. Pathologic examination of the biopsy or resection specimen can help in identification of unsuspected cases of certain forms of hereditary CRC due to the characteristic morphologic findings. Additional immunohistochemical and molecular studies can then provide a definitive diagnosis. The most common form of hereditary CRC is Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) which is characterized by proximally located tumors frequently showing mucinous and medullary type histologic features. The syndrome results from a germline mutation in genes for mismatch repair (MMR) proteins leading to insufficient DNA repair and development of tumors characterized by high levels of instability in short tandem repeat DNA sequences (microsatellites) or "microsatellite instability-high" (MSI-H). The presence of intra-epithelial lymphocytes is single most helpful morphologic feature in identification of CRC caused by deficiency in MMR proteins, for which MSI-H status is a good marker but morphologic features and MSI-H do not differentiate tumors caused by germline mutations in one of the MMR genes (Lynch syndrome) from sporadic CRC due to inactivation of MLH-1 through promoter methylation. Hereditary CRC may also arise in various familial polyposis syndromes which include familial adenomatous polyposis (FAP), attenuated FAP and other multiple adenomas syndromes as well as various hamartomatous polyposis syndromes. All of these rare conditions have characteristic clinical presentation and histopathologic features of polyps and most of them have defined genetic abnormality. Furthermore, due to the germline nature of mutations in these syndromes, various extracolonic manifestations may be the first sign of the disease and knowledge of such associations can greatly improve the quality of care for these patients. The role of pathologist is to recognize these characteristics and initiate appropriate follow up with clinicians and genetic counselors.

Authors+Show Affiliations

Department of Pathology, Creighton University Medical Center, Omaha, NE 68131, USA. zorangatalica@creighton.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17564815

Citation

Gatalica, Zoran, and Emina Torlakovic. "Pathology of the Hereditary Colorectal Carcinoma." Familial Cancer, vol. 7, no. 1, 2008, pp. 15-26.
Gatalica Z, Torlakovic E. Pathology of the hereditary colorectal carcinoma. Fam Cancer. 2008;7(1):15-26.
Gatalica, Z., & Torlakovic, E. (2008). Pathology of the hereditary colorectal carcinoma. Familial Cancer, 7(1), 15-26.
Gatalica Z, Torlakovic E. Pathology of the Hereditary Colorectal Carcinoma. Fam Cancer. 2008;7(1):15-26. PubMed PMID: 17564815.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathology of the hereditary colorectal carcinoma. AU - Gatalica,Zoran, AU - Torlakovic,Emina, Y1 - 2007/06/13/ PY - 2007/04/16/received PY - 2007/05/14/accepted PY - 2007/6/15/pubmed PY - 2008/7/9/medline PY - 2007/6/15/entrez SP - 15 EP - 26 JF - Familial cancer JO - Fam. Cancer VL - 7 IS - 1 N2 - Positive familial history (first or second degree relative) for colorectal carcinoma (CRC) can be found in approximately 30% of all newly diagnosed cases, but less than 5% will be due to a defined genetic category of hereditary CRC. Pathologic examination of the biopsy or resection specimen can help in identification of unsuspected cases of certain forms of hereditary CRC due to the characteristic morphologic findings. Additional immunohistochemical and molecular studies can then provide a definitive diagnosis. The most common form of hereditary CRC is Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) which is characterized by proximally located tumors frequently showing mucinous and medullary type histologic features. The syndrome results from a germline mutation in genes for mismatch repair (MMR) proteins leading to insufficient DNA repair and development of tumors characterized by high levels of instability in short tandem repeat DNA sequences (microsatellites) or "microsatellite instability-high" (MSI-H). The presence of intra-epithelial lymphocytes is single most helpful morphologic feature in identification of CRC caused by deficiency in MMR proteins, for which MSI-H status is a good marker but morphologic features and MSI-H do not differentiate tumors caused by germline mutations in one of the MMR genes (Lynch syndrome) from sporadic CRC due to inactivation of MLH-1 through promoter methylation. Hereditary CRC may also arise in various familial polyposis syndromes which include familial adenomatous polyposis (FAP), attenuated FAP and other multiple adenomas syndromes as well as various hamartomatous polyposis syndromes. All of these rare conditions have characteristic clinical presentation and histopathologic features of polyps and most of them have defined genetic abnormality. Furthermore, due to the germline nature of mutations in these syndromes, various extracolonic manifestations may be the first sign of the disease and knowledge of such associations can greatly improve the quality of care for these patients. The role of pathologist is to recognize these characteristics and initiate appropriate follow up with clinicians and genetic counselors. SN - 1389-9600 UR - https://www.unboundmedicine.com/medline/citation/17564815/Pathology_of_the_hereditary_colorectal_carcinoma_ L2 - https://doi.org/10.1007/s10689-007-9146-8 DB - PRIME DP - Unbound Medicine ER -